Electricity sparks neuronal diversity during brain development

The cerebral cortex is a highly developed brain region, which allows intellectual functions such as conscious perception, anticipation of events and language. These functions are mediated by specific sets of neuronal circuits. To understand how these circuits emerge during development, researchers from the University of Geneva (UNIGE), Switzerland, in collaboration with an american team, investigated what enables neuronal stem cells to generate successive subtypes of neurons as the embryo grows. By measuring the electrical activity of these progenitors, they found that akin to a battery getting charged, membrane voltage values increase as the embryo develops and new neurons are being created. To test the role of this electrical charge, neuroscientists experimentally manipulated progenitor voltage values, which allowed them to select which type of neuron was being born. These results, published in Cell, reveal an unexpected role for bioelectric cell properties in the generation of neuronal diversity.

The cerebral cortex is characterized by a diversity of neuronal cell type which assemble during development to form circuits, underlying functions such as skilled movements and sensory integration. These circuits emerge in two stages: first during embryogenesis, when neurons are born, and later on after we are born, when neurons contact each other to form circuits that are chiseled by the environment.

In the embryo, different types of cortical neurons are sequentially created in a well-defined order by stem cells called neuronal progenitors, located deep within the brain. "We wondered how these progenitors were able to know what type of neurons to make at each embryonic age," explains Denis Jabaudon, professor in the Department of Basic Neurosciences at the Faculty of Medicine of the UNIGE.

Electricity drives progenitor behaviour

To address this question, the UNIGE team took an unusual approach. "Usually genes are considered as the stars of cellular development, explains Ilaria Vitali, a researcher in the team. Here, we focused on another player, the electrical properties of these progenitors." While the role of electrical properties in the normal workings of neuronal circuits is well established, there was until now only little information on a role for electrical charge in progenitor properties. Using a pipette smaller than two microns in diameter to pierce the cell membrane, the neuroscientists were able to measure the electrical charge of neuronal progenitors as the cortex was forming in mouse embryos. "What we found is that as the embryo grows and the types of neurons generate become more complex, progenitor voltage values increased," says Denis Jabaudon.

An electrical switch to generate distinct neuronal subtypes

To manipulate this process, the scientists next genetically modified embryonic cells. "We expressed small synthetic channels at the surface of the progenitors, which allowed us to manipulate their voltage at will by charging or discharging these cells," explains Sabine Fièvre, a co-author in the study and researcher in the UNIGE team. "And it turns out that if the progenitors are artificially charged early in embryogenesis, they prematurely generate normally later-born neurons." "Conversely, if we discharge the progenitors, they generate neurons that are normally born earlier in the embryo's life," adds Denis Jabaudon.

These results demonstrate that the bioelectric activity of progenitors plays a central role in generating neuronal diversity. This could help explain how some neurological disorders associated with abnormal electrical activity, such as epilepsy, affect brain development during embryogenesis.

-end-

Université de Genève

Related Neurons Articles:

The first 3D map of the heart's neuronsAn interdisciplinary research team establishes a new technological pipeline to build a 3D map of the neurons in the heart, revealing foundational insight into their role in heart attacks and other cardiac conditions.

Mood neurons mature during adolescenceResearchers have discovered a mysterious group of neurons in the amygdala -- a key center for emotional processing in the brain -- that stay in an immature, prenatal developmental state throughout childhood.

Connecting neurons in the brainLeuven researchers uncover new mechanisms of brain development that determine when, where and how strongly distinct brain cells interconnect.

Trending Science News

Top Science Podcasts

Clint SmithThe killing of George Floyd by a police officer has sparked massive protests nationwide. This hour, writer and scholar Clint Smith reflects on this moment, through conversation, letters, and poetry.

#562 Superbug to BedsideBy now we're all good and scared about antibiotic resistance, one of the many things coming to get us all. But there's good news, sort of. News antibiotics are coming out! How do they get tested? What does that kind of a trial look like and how does it happen? Host Bethany Brookeshire talks with Matt McCarthy, author of "Superbugs: The Race to Stop an Epidemic", about the ins and outs of testing a new antibiotic in the hospital.

GrahamIf former Minneapolis police officer Derek Chauvin's case for the death of George Floyd goes to trial, there will be this one, controversial legal principle looming over the proceedings: The reasonable officer.
In this episode, we explore the origin of the reasonable officer standard, with the case that sent two Charlotte lawyers on a quest for true objectivity, and changed the face of policing in the US.
This episode was produced by Matt Kielty with help from Kelly Prime and Annie McEwen.
Support Radiolab today at Radiolab.org/donate.